Yu　TC,　Junger　WG,　Yuan　CJ,　Jin　A,　Zhao　Y,　Zheng　XQ,　Zeng　YJ,　Liu　JG.　Shockwaves　increase　T-cell　proliferation　and　IL-2　expression　through　ATP　release,　P2X7　receptors,　and　FAK　activation.　Am　J　Physiol　Cell　Physiol　298:　C457-C464,　2010.　First　published　November　4,　2009;　doi:　10.1152/ajpcell.00342.2009.-Shockwaves　elicited　by　transient　pressure　disturbances　are　used　to　treat　musculoskeletal　disorders.　Previous　research　has　shown　that　shockwave　treatment　affects　T-cell　function,　enhancing　T-cell　proliferation　and　IL-2　expression　by　activating　p38　mitogen-activated　protein　kinase　(MAPK)　signaling.　Here　we　investigated　the　signaling　pathway　by　which　shockwaves　mediate　p38　MAPK　phosphorylation.　We　found　that　shockwaves　at　an　intensity　of　0.18　mJ/mm(2)　induce　the　release　of　extracellular　ATP　from　human　Jurkat　T-cells　at　least　in　part　by　affecting　cell　viability.　ATP　released　into　the　extracellular　space　stimulates　P2X7-type　purinergic　receptors　that　induce　the　activation　of　p38　MAPK　and　of　focal　adhesion　kinase　(FAK)　by　phosphorylation　on　residues　Tyr397　and　Tyr576/577.　Elimination　of　released　ATP　with　apyrase　or　inhibition　of　P2X7　receptors　with　the　antagonists　KN-62　or　suramin　significantly　weakens　FAK　phosphorylation,　p38　MAPK　activation,　IL-2　expression,　and　T-cell　proliferation.　Conversely,　addition　of　exogenous　ATP　causes　phosphorylation　of　FAK　and　p38　MAPK.　Silencing　of　FAK　expression　also　reduces　these　cell　responses　to　shockwave　treatment.　We　conclude　that　shockwaves　enhance　p38　MAPK　activation,　IL-2　expression,　and　T-cell　proliferation　via　the　release　of　cellular　ATP　and　feedback　mechanisms　that　involve　P2X7　receptor　activation　and　FAK　phosphorylation.